title: Docking and quantitative structure-activity relationship of oxadiazole derivates as inhibitors of GSK3β.
abstract: The binding modes of 42 oxadiazole derivates inside glycogen synthase kinase 3 beta (GSK3β were determined using docking experiments; thus, the preferred active conformations of these inhibitors are proposed. We found that these compounds adopt a scorpion-shaped conformation and they accept a hydrogen bond (HB) from the residue Val135 of the GSK3β ATP-binding site hinge region. In addition, quantitative structure-activity relationship (QSAR) models were constructed to explain the trend of the GSK3β inhibitory activities for the studied compounds. In a first approach, three-dimensional (3D) vectors were calculated using docking conformations and, by using multiple-linear regression, we assessed that GETAWAY vectors were able to describe the reported biological activities. In other QSAR approach, SMILES-based optimal descriptors were calculated. The best model included three-SMILES elements SSSβ leading to the identification of key molecular features that contribute to a high GSK3β inhibitory activity.
authors.affiliation: Centro de Bioinformática y Simulación Molecular, Facultad de Ingeniería, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile.
authors.forename: Luisa
authors.initials: L
authors.lastname: Quesada-Romero
authors.forename: Julio
authors.initials: J
authors.lastname: Caballero
mesh_terms: D003198:Computer Simulation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D062105:Molecular Docking Simulation; D010069:Oxadiazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D010069:Oxadiazoles; D047428:Protein Kinase Inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3